DESCRIPTION (from the abstract): The overall goal of this project is to facilitate the discovery and implementation of rational therapy for HD by careful analysis of the unique clinical data generated in the Clinical Core, defining the determinants of the course of HD. This will be accomplished by examining three different sets of hypotheses. In Specific Aim 1, we will test the hypothesis that CAG repeat number and other variables can be used to develop accurate models of the onset and course of HD. We hypothesize that CAG repeat length has a small but significant influence on the rate of disease progression. We will also test the hypothesis that familial factors in addition to CAG repeat length affect the course of HD. In Specific Aim 2, we will characterize neuropsychological features of early HD, and correlates of clinical and brain abnormalities. In Specific Aim 3, we will use a novel robotic system for defining the progressive motor disorder in HD expansion positive individuals and HD patients. In Specific Aim 4, we will test the hypothesis that diseases similar to HD are also caused by CAG expansion mutations. We will identify the genetic etiology of one of these diseases. In summary, we will provide new approaches for understanding HD?s clinical course, which will provide clues to pathogenesis and the development of novel treatment strategies.